Objective: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. Design: In KIMS (Pfizer International Metabolic Database) 13 983 GH-deficient patients with 69 056 patient-years of follow-up were available. Methods: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P!0.05. Results: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at followup, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (PZ0.017) and malignancies (PZ0.044). Conclusions: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.

GH deficiency (GHD) in adulthood is accompanied by physical and psychological impairments. One hundred fifteen patients (67 male, 48 female) with pronounced GHD were enrolled in a randomized, double-blind, placebo-controlled study with objectives that included effects on body composition, cardiac structure, and function and safety of replacement therapy with recombinant human GH (Saizen). Sixty patients (31 male, 29 female) received GH at a dose of 0.005-0.010 mg/kg.d, and 55 patients (36 male, 19 female) received placebo for 6 months. Assessment of body composition by dual-energy x-ray absorptiometry demonstrated a treatment difference in lean body mass increase of 2.1 kg (between-group comparison, P < 0.0001), which was significantly greater among males than females (P < 0.0001) [males: GH, +3.13 kg (2.42, 3.84); placebo, +0.11 kg (-0.60, 0.82); and females: GH, +0.64 kg (-0.15, 1.44); placebo: -0.90 kg (-2.20, 0.39)] [mean change 0-6 months (95% confidence limits)] and was associated with IGF-I changes. The decrease in fat mass of 2.8 kg (between-group comparison, P < 0.0001) noted by DEXA was also evident from bioelectric impedance and anthropometric measurements. Echocardiography showed comparable improvement in left ventricular systolic function after GH treatment in both genders. End-systolic volume decreased by 4.3 +/- 10.5 ml (from 35.8 +/- 17.6 ml; between-group comparison, P = 0.035) and ejection fraction increased by 5.1 +/- 10.0% (from 55.0 +/- 11.2%; between-group comparison, P = 0.048), approaching normalcy. Diastolic function did not change as assessed by isovolumic relaxation time, early diastolic flow, diastolic flow secondary to atrial contraction, or ratio of peak mitral early diastolic and atrial contraction velocity. GH treatment was well tolerated, with adverse events primarily related to effects on fluid balance. No apparent relationship between IGF-I levels and the occurrence or severity of adverse events was identified. In conclusion, GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females. In contrast, cardiac function improvement appears to benefit both genders equally.

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